| Autor: |
Osbourn, M, Soares, DC, Vacca, F, Cohen, ES, Scott, IC, Gregory, WF, Smyth, DJ, Toivakka, M, Kemter, AM, le, Bihan T, Wear, M, Hoving, D, Filbey, KJ, Hewitson, JP, McSorley, HJ |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Zdroj: |
Osbourn, M, Soares, DC, Vacca, F, Cohen, ES, Scott, IC, Gregory, WF, Smyth, DJ, Toivakka, M, Kemter, AM, le, B T, Wear, M, Hoving, D, Filbey, KJ, Hewitson, JP & McSorley, HJ 2017, ' HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33. ', Immunity . https://doi.org/10.1016/j.immuni.2017.09.015 |
| DOI: |
10.1016/j.immuni.2017.09.015 |
| Popis: |
Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine’s activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
